FDA red and green lights: October 2024

Novartis's Scemblix, whose US label was on Tuesday extended from third-line to front-line chronic myelogenous leukaemia, has rounded out the FDA's oncology approvals for October, a month in which the agency also greenlit three other cancer drugs.

One approval that didn’t come involved Amgen’s KRAS G12C inhibitor Lumakras, however. That drug was due a decision by 17 October in chemo-refractory colorectal cancer in combination with Vectibix, but this was extended by three months so the FDA could review supplemental data. Lumakras's new PDUFA date here is 17 January 2025.

This means that Amgen has fallen further behind Bristol Myers Squibb, which got an accelerated green light for Krazati plus Erbitux in second-line colorectal cancer in June. Also still unresolved are additional approval decisions over BeiGene's Tevimbra in first-line oesophageal squamous cell carcinoma, and Incyte/Novartis's Jakafi for paediatric GvHD.

Both had been expected in July, but Tevimbra is delayed pending deliberations over the approvability of PD-(L)1 drugs in stomach cancer discussed at a September adcom. As for Jakafi, Novartis most recently said this approval was expected in the fourth quarter.

Practice-changing?

Scemblix's first-line CML nod was perhaps unsurprising, given the supporting ASC4First study's results, presented during this year's ASCO conference, being described as practice-changing. This was despite the trial using the surrogate endpoint of major molecular response (MMR), rather than survival; MMR is seen as predictive of long-term outcomes, and has backed other first-line CML approvals.

Perhaps more surprising, however, was the FDA's decision not to grant Scemblix full approval, but rather a conditional green light on an accelerated basis. Thus the nod is "contingent on ... clinical benefit from confirmatory evidence", which might include PFS and OS data; both are secondary endpoints in ASC4First.

October's other US oncology approvals include Roche's PI3Kα inhibitor inavolisib, which as Itovebi has a chance to challenge Novartis's Piqray in ER-positive, HER2-negative PIK3CA-mutated breast cancer.

Also notable is Astellas's Vyloy (zolbetuximab), which at the second time of asking became the first ever drug targeting Claudin18.2 to obtain an FDA green light. That approval came after a complete response letter in January, in which the FDA cited deficiencies at a third-party manufacturer; Astellas managed to resolve the problems quickly, and resubmitted the filing in May.

Selected October 2024 US regulatory decisions in oncology

Source: OncologyPipeline.